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CD, a once per day oral formulation of diltiazem based on Elan's spheroidal oral drug absorption system and marketed by Marion Merrel Dow; Duragesic, a transdermal fentanyl patch developed by Alza and marketed by Janssen Pharmaceutica in 1991; Efidac/24, a once a day antihistamine based on Alza's Oros technology and marketed by Ciba Geigy in 1993; Minipress XL, a once per day antihypertensive formulation of prazosin based on Alza's Oros technology and marketed by Pfiser; and Testoderm, a transdermal patch of the male hormone testosterone, developed and marketed by Alza in 1993. Four transdermal patches delivering nicotine (Nicoderm, Alza-Marion Merrel Dow; Habitrol, Lohmann-Ciba; Prostep, Elan-Lederle; and Nicotrol, Cygnus-McNeil) were introduced in 1992. Procardia XL is a once-per-day oral formulation of the calcium channel blocker Nifedipine based on Alza's Oros osmotic technology, and Dilacor XR is a one-per-day oral formulation of diltiazem, based on Jago's Geometrix technology. Three of these products are discussed below in more detail. |
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1. Nicotine Transdermal Patch |
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In 1992 four Nicotine Transdermal Systems were introduced as aids to smoking cessation. The need for a system to alleviate the physical nicotine withdrawal symptoms was so great that the USA product sales for 1992 were over $600 million. |
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The transdermal nicotine patches were developed to continuously deliver low levels of nicotine to the systemic circulation, under the hypothesis that they would reduce the withdrawal symptoms and allow the smoker to concentrate on the behavioral aspects of the addiction. Habitrol, the leading nicotine system is a round, flat, 0.6 mm thick multilayer unit. Proceeding from the visible surface toward the surface attached to the skin are (a) a tan-colored aluminized backing film; (b) a pressure sensitive acrylate adhesive; (c) a layer containing a methacrylic acid copolymer solution of nicotine dispersed in a pad of nonwoven viscose and cotton; (d) an adhesive layer similar in composition to (b) above; and (e) a protective aluminized release liner that overlays the adhesive layer and must be removed prior to use [132]. |
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Pharmacokinetic studies for all patches [133137], comparison of the kinetics of skin patches versus the Nicorette Gum [138], effect of application site [139], and comparison of the kinetics of the four commercial patches [140] have been performed. Clinical, multicenter, and double blinded studies have been performed [141143] showing that the Quit Rates were higher for those smokers using nicotine patches versus those using controls. In clinical trials where concomitant support was given, the Quit Rates in general were substantially higher with the groups using nicotine patches giving the best results. The patches were well tolerated, with mild itchiness and redness being the most common complaint [144]. |
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